The incidence of many forms of cancer is expected to increase as the population ages. For example, prostate cancer is the most commonly diagnosed cancer in United States men as well as the second reading cause of male cancer deaths. It is projected that in 1994 there will be 200,000 new cases of prostate cancer diagnosed as well as 38,000 deaths from prostate cancer and these numbers are expected to continue to rise as the population ages. Approximately 50% of patients diagnosed with prostate cancer have disease which has or will escape the prostate. Prostate cancer metastasizes to the skeletal system and patients typically die with overwhelming osseous metastatic disease. As yet, there is no effective curative therapy and very little palliative therapy for patients with metastatic disease.
The process of tumor cell metastasis requires that cells depart from the primary tumor, invade the basement membrane, traverse through the bloodstream from tumor cell emboli, interact with the vascular endothelium of the target organ, extravasate, and proliferate to form secondary tumor colonies as described by E. C. Kohn, Anticancer Re., 13, 2553 (1993); and L. A. Kiotta, P. S. Steeg, W. G. Stettler-Stevenson, Cell 64, 327 (1991).
It is generally accepted that many stages of the metastatic cascade involve cellular interactions mediated by cell surface components such as carbohydrate-binding proteins, which include galactoside binding lectins (galectins) as described by A. Raz, R. Lotan, Cancer Metastasis Rev. 6, 433 (1987); and H. J. Gabius, Biochim Biophys Acta 1071, 1 (1991). Treatment of B16 melanoma and uv-2237 fibrosarcoma cells in vitro with anti-galectin monoclonal antibodies prior to their intravenous (i.v.) injection into the tail vein of syngeneic mice resulted in a marked inhibition of tumor lung colony development as described by L. Meromsky, R. Lotan, A. Raz, Cancer Res. 46, 5270 (1991). Transfection of low metastatic, low galectin-3 expressing uv-2237-c115 fibrosarcoma cells with galectin-3 cDNA resulted in an increase of the metastatic phenotype of the transfected cells as described by A. Raz, D. Zhu, V. Hogan, J. Shah, T. Raz, R. Karkash, G. Pazerini, P. Carmi, Int. J Cancer 46, 871 (1990). Furthermore, a correlation has been established between the level of galectin-3 expression in human papillary thyroid carcinoma and tumor stage of human colorectal and gastric carcinomas as described by L. Chiariotti, M. T. Berlinjieri, P. DeRosa, C. Battaglia, N. Berger, C. B. Bruni, A. Fusco, Omeogene 7, 2507 (1992); L. Irimura, Y. Matsushite, R. C. Sutton, D. Carralero, D. W. Ohanesian, K. R. Cleary, D. M. Ota, Int J Cancer 51, 387 (1991); R. Lotan, H. Ito, W. Yasui, H. Yokozak, D. Lotan, E. Tahara, Int J Cancer 56, 474 (1994); and M. M. Lotz, C. W. Andrews, C. A. Korzelius, E. C. Lee, G. D. Steele, A. Clarke, A. M. Mercurio, PNAS, USA 90, 3466 (1993).
Simple sugars such as methyl-alpha-D lactoside and lacto-N-tetrose have been shown to inhibit metastasis of B16 melanoma cells, while D-galactose and arabinogalactose inhibited liver metastasis of L-1 sarcoma cells as described by J. Beauth et al., J Cancer Res Clin Oncol 113, 51 (1987).
It is known that intravenous injection of B16-F1 murine melanoma cells with citrus pectin or modified citrus pectin into syngenic mice resulted in a significant increase or decrease of lung colonization, respectfully as described by D. Platt and A. Raz, J. Natl Cancer Inst. 84:438-42 (1992). Prior to the discovery disclosed herein, an effective treatment for inhibiting cancer metastasis utilizing a non-cytotoxic agent by oral administration did not exist. Thus, a need exists for a therapy which is based on the oral administration of an non-cytotoxic agent.